Opportunities and Limitations of Renal Denervation: Where Do We Stand?

Hypertension is a primary contributor to cardiovascular disease, and the leading risk factor for loss of quality adjusted life years. Up to 50% of the cases of hypertension in the United States remain uncontrolled. Additionally, 8%-18% of the hypertensive population have resistant hypertension; uncontrolled pressure despite 3 different antihypertensive agents. Recently, catheter-based percutaneous renal denervation emerged as a method for ablating renal sympathetic nerves for difficult-to-control hypertension. Initial randomized (non-sham) trials and registry analyses showed impressive benefit, but the first sham-controlled randomized controlled trial using monopolar radiofrequency ablation showed limited benefit. With refinement of techniques to include multipolar radiofrequency, ultrasound denervation, and direct ethanol injection, randomized controlled trials demonstrated significant blood pressure improvement, leading to US Food and Drug Administration approval of radiofrequency- and ultrasound-based denervation technologies. In this review article, we summarize the major randomized sham-controlled trials and societal guidelines regarding the efficacy and safety of renal artery denervation for the treatment of uncontrolled hypertension.

Impella Versus Intra-Aortic Balloon Pump in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: An Observational Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra-aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA-ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA-ECMO. METHODS AND RESULTS: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA-ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; P-trend<0.001). In-hospital mortality was higher with ECMO with Impella (54.8%) compared with ECMO only (50.4%) and ECMO with IABP (48.4%). After adjustment, ECMO with IABP versus ECMO only was associated with lower in-hospital mortality (adjusted odds ratio [aOR], 0.83; P=0.02). ECMO with Impella versus ECMO only had similar in-hospital mortality (aOR, 1.09; P=0.695) but was associated with more bleeding (aOR, 1.21; P=0.007) and more acute kidney injury requiring hemodialysis (aOR, 1.42; P<0.001). ECMO with Impella versus ECMO with IABP was associated with greater risk of acute kidney injury requiring hemodialysis (aOR, 1.49; P=0.002), higher in-hospital mortality (aOR, 1.32; P=0.001), and higher 40-day mortality (hazard ratio, 1.25; P<0.001). CONCLUSIONS: In patients with cardiogenic shock on VA-ECMO, LVU with Impella, particularly with 2.5/CP, was not associated with improved survival at 40 days but was associated with increased adverse events compared with IABP. More data are needed to assess Impella platform-specific comparative outcomes of LVU.

Nationwide trends of balloon pulmonary angioplasty and pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (2012-2019).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of a pulmonary embolus that occurs in approximately 1%-3% of patients. Pulmonary thromboendoarterectomy (PTE) can be a curative procedure, but balloon pulmonary angioplasty (BPA) has emerged as an option for poor surgical candidates. We used the National Inpatient Sample to query patients who underwent PTE or BPA between 2012 and 2019 with CTEPH. The primary outcome was a composite of in-hospital mortality, myocardial infarction, stroke, tracheostomy, and prolonged mechanical ventilation. Outcomes were compared between low- and high-volume centers, defined as 5 and 10 procedures per year for BPA and PTE, respectively. During our study period, 870 BPA and 2395 PTE were performed. There was a 328% relative increase in the number of PTE performed during the study period. Adverse events for BPA were rare. There was an increase in the primary composite outcome for low-volume centers compared to high-volume centers for PTE (24.4% vs. 12.1%, p = 0.003). Patients with hospitalizations for PTE in low-volume centers were more likely to have prolonged mechanical ventilation (20.0%% vs. 7.2%, p < 0.001) and tracheostomy (7.8% vs. 2.6%, p = 0.017). In summary, PTE rates have been rising over the past 10 years, while BPA rates have remained stable. While adverse outcomes are rare for BPA, patients with hospitalizations at low-volume centers for PTE were more likely to have adverse outcomes. For patients undergoing treatment of CTEPH with BPA or PTE, referral to high-volume centers with multidisciplinary teams should be encouraged for optimal outcomes.

Randomized Trials of Renal Denervation for Uncontrolled Hypertension: An Updated Meta-Analysis.

BACKGROUND: Despite optimal medical therapy, a significant proportion of patients' blood pressure remains uncontrolled. Catheter-based renal denervation (RDN) has been proposed as a potential intervention for uncontrolled hypertension. We conducted an updated meta-analysis to assess the efficacy and safety of RDN in patients with uncontrolled hypertension, with emphasis on the differential effect of RDN in patients on and off antihypertensive medications. METHODS AND RESULTS: Online databases were searched to identify randomized clinical trials comparing efficacy and safety of RDN versus control in patients with uncontrolled hypertension. Subgroup analyses were conducted for sham-controlled trials and studies that used RDN devices that have gained or are currently seeking US Food and Drug Administration approval. Fifteen trials with 2581 patients (RDN, 1723; sham, 858) were included. In patients off antihypertensive medications undergoing RDN, a significant reduction in 24-hour ambulatory (-3.70 [95% CI, -5.41 to -2.00] mm Hg), office (-4.76 [95% CI, -7.57 to -1.94] mm Hg), and home (-3.28 [95% CI, -5.96 to -0.61] mm Hg) systolic blood pressures was noted. In patients on antihypertensive medications, a significant reduction was observed in 24-hour ambulatory (-2.23 [95% CI, -3.56 to -0.90] mm Hg), office (-6.39 [95% CI, -11.49 to -1.30]), home (-6.08 [95% CI, -11.54 to -0.61] mm Hg), daytime (-2.62 [95% CI, -4.14 to -1.11]), and nighttime (-2.70 [95% CI, -5.13 to -0.27]) systolic blood pressures, as well as 24-hour ambulatory (-1.16 [95% CI, -1.96 to -0.35]), office (-3.17 [95% CI, -5.54 to -0.80]), and daytime (-1.47 [95% CI, -2.50 to -0.27]) diastolic blood pressures. CONCLUSIONS: RDN significantly lowers blood pressure in patients with uncontrolled hypertension, in patients off and on antihypertensive medications, with a favorable safety profile. The efficacy of RDN was consistent in sham-controlled trials and contemporary trials using US Food and Drug Administration-approved devices.

Sex Disparities in the Management, Outcomes, and Transfer of Patients Hospitalized for Cardiogenic Shock.

Background: Previous studies have shown that women have worse outcomes for cardiogenic shock (CS) than men. Patients who receive care in CS "hubs" have also been shown to have improved outcomes when compared to those treated at "spokes." This study aimed to examine the presence of sex disparities in the outcomes of CS in relation to hospital type. Methods: Hospitalizations of adults with a diagnosis of CS were identified using data from the 2016-2019 Nationwide Readmissions Database. CS "hubs" were defined as any centers receiving at least 1 interhospital transfer with CS, while those without such transfers were classified as "spokes." Data were combined across years and multivariable logistic regression modeling was used to evaluate the association of sex with in-hospital mortality, invasive procedures, and transfer to hubs. Results: There were a total of 618,411 CS hospitalizations (62.2% men) with CS related to acute myocardial infarction comprising 15.3 to 17.3% of women hospitalizations and 17.8 to 20.3% of men hospitalizations. In-hospital mortality was lower at hubs (34.5% for direct admissions, 31.6% for transfers) than at spokes (40.3%, all P < .01). Women underwent fewer invasive procedures (right heart catheterization, percutaneous coronary intervention, mechanical circulatory support) and had higher mortality than men. Female sex was independently associated with decreased transfers to hubs (odds ratio, 0.93; 95% CI, 0.89-0.96) and increased mortality (odds ratio, 1.09; 95% CI, 1.05-1.12). Conclusions: Women with CS were less likely to be treated at a hub or transferred to a hub, had higher in-hospital mortality, and had a lower likelihood of receiving CS-related procedures than men. Further research is needed to understand sex-specific gaps in CS outcomes.

Feasibility and Safety of Impella-Assisted High-Risk PCI Before TAVR in Patients With Severe Aortic Stenosis.

Background: There are limited data on the feasibility of Impella-assisted percutaneous coronary intervention (PCI) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods: To assess the feasibility of the Impella-assisted PCI in patients with severe symptomatic AS, we retrospectively reviewed the medical records to identify patients who were electively admitted for Impella-assisted PCI with a subsequent TAVR at Weill Cornell Medical Center from 2016 to 2021. Results: During the study period, 15 patients were identified to be eligible for the study, but the Impella failed to cross the aortic valve in 1 patient despite a concomitant balloon aortic valvuloplasty requiring a switch to an intra-aortic balloon pump to assist PCI. A total of 14 patients underwent successful PCI with the Impella CP and were included in the analysis. The median age was 89 years, and women accounted for 43% of the cohort. The median aortic valve area and mean gradient were 0.85 cm2 and 40 mm Hg, respectively, with a median left ventricular ejection fraction of 51%. The median SYNTAX score was 13. The left main stent was placed in 6 patients (43%), with a rotational atherectomy performed in 10 patients (71%). The balloon aortic valvuloplasty was performed in 2 patients before Impella placement. The TAVR was performed in all 14 patients on a median post-Impella-assisted PCI day of 25. No procedural complications were noted post-TAVR with no in-hospital or 30-day death. Conclusions: In this single-center study of patients with severe AS, the elective Impella-assisted high-risk PCI was feasible and safe before TAVR in selected patients.

Impact of Socioeconomic Status on Mechanical Circulatory Device Utilization and Outcomes in Cardiogenic Shock.

Objectives: This study evaluates the impact of socioeconomic status (SES) on utilization of mechanical circulatory support (MCS) devices and outcomes in cardiogenic shock (CS). Background: CS is associated with significant mortality. There is increasing use of temporary MCS devices in CS, and its impact on outcomes is currently under investigation. There is a lack of data on the effect of SES on the utilization of MCS devices in CS. Methods: CS hospitalizations were obtained from the State Inpatient Databases in 2016 from 9 states representing various regions in the United States. The study had exempt institutional review board status as the database includes deidentified data. Hospitalizations were separated into SES cohorts based on the median household income of the patient residence zip code. Utilization of MCS devices and revascularization procedures along with clinical outcomes with CS were compared across the quartiles. Results: There were 38,520 hospitalizations identified with CS, 42.6% of which were secondary to acute myocardial infarction. Patients from higher SES areas were significantly older but had lower burden of comorbidities. Utilization of temporary MCS devices was higher for hospitalizations from higher SES regions (frequency from the lowest SES quartile to the highest SES quartile: 21.3%, 21.5%, 23.5, and 24.1%, P < .01), though revascularization rates were similar. However, there was no significant difference in overall mortality from CS among the 4 quartiles. Patients from regions of higher SES experienced increased hospital costs. Conclusions: Higher SES regions had increased use of temporary MCS. There was no difference in mortality between SES cohorts.

Racial Disparities in Access to High-Volume Mitral Valve Transcatheter Edge-to-Edge Repair Centers.

Background: Severe mitral regurgitation is a progressive disease associated with high morbidity and mortality, and frequent readmissions for heart failure. Surgical mitral valve repair or replacement has been the gold-standard treatment; however, advances in transcatheter edge-to-edge repair (TEER) have provided alternatives for high-risk surgical patients. There are no data on racial disparities in access to high-volume TEER centers. Methods: Data on TEER hospitalizations from New York, New Jersey, Maryland, North Carolina, Washington, Colorado, Arizona, and Florida were analyzed using the State Inpatient Databases for 2016. The baseline characteristics of patients who underwent TEER at high- (≥25 procedures per year) and low-volume centers were identified. The association between race and the likelihood of undergoing TEER at high-volume centers was assessed. The secondary outcomes were mortality and the frequency of home discharges. Results: Of 1567 patients included in the analysis, 1129 underwent TEER at high-volume centers. Patients treated at high-volume centers had a higher prevalence of chronic kidney disease and congestive heart failure. Black and Hispanic patients were 59% (adjusted odds ratio [OR], 0.41; P < .001) and 51% (adjusted OR, 0.49; P < .001) less likely to undergo TEER at high-volume centers, respectively, compared with White patients. Hispanic patients were 3 times more likely to die during index admission than White patients (adjusted OR, 3.32; P = .027). There was geographic clustering of TEER centers, and a higher ratio of White patients to minority patients in zip codes with high-volume TEER centers. Conclusions: Racial minorities patients, particularly Black and Hispanic patients, are less likely to undergo TEER at high-volume centers. Hispanic patients experience higher rates of in-hospital mortality after TEER than White patients.